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International Journal of Molecular... Mar 2024The brain is susceptible to oxidative stress, which is associated with various neurological diseases. Edaravone (MCI-186, 3-methyl-1 pheny-2-pyrazolin-5-one), a free... (Review)
Review
The brain is susceptible to oxidative stress, which is associated with various neurological diseases. Edaravone (MCI-186, 3-methyl-1 pheny-2-pyrazolin-5-one), a free radical scavenger, has promising effects by quenching hydroxyl radicals (∙OH) and inhibiting both ∙OH-dependent and ∙OH-independent lipid peroxidation. Edaravone was initially developed in Japan as a neuroprotective agent for acute cerebral infarction and was later applied clinically to treat amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. There is accumulating evidence for the therapeutic effects of edaravone in a wide range of diseases related to oxidative stress, including ischemic stroke, ALS, Alzheimer's disease, and placental ischemia. These neuroprotective effects have expanded the potential applications of edaravone. Data from experimental animal models support its safety for long-term use, implying broader applications in various neurodegenerative diseases. In this review, we explain the unique characteristics of edaravone, summarize recent findings for specific diseases, and discuss its prospects for future therapeutic applications.
Topics: Animals; Female; Pregnancy; Amyotrophic Lateral Sclerosis; Antioxidants; Antipyrine; Edaravone; Free Radical Scavengers; Neurodegenerative Diseases; Neuroprotective Agents; Placenta
PubMed: 38474192
DOI: 10.3390/ijms25052945 -
Cureus Jun 2023Sickle cell hemoglobinopathies encompass a range of qualitative and quantitative hemoglobin disorders that are inherited genetically. This group of disorders includes... (Review)
Review
Sickle cell hemoglobinopathies encompass a range of qualitative and quantitative hemoglobin disorders that are inherited genetically. This group of disorders includes sickle cell beta thalassemia, sickle cell trait, and sickle cell disease (SCD). Globally, SCD is the most common disorder. Even epidemiological data suggests the majority of diseases, as well as traits, are concentrated in Sub-Saharan Africa, North-East Africa, the Middle East, and India. The physiological changes in pregnancy predispose to an increased risk of catastrophic events like a vaso-occlusive crisis, thromboembolic events, and their related sequelae, leading eventually to villous infarction, necrosis, and fibrosis leading to compromising uteroplacental circulation. Conversely, the mother may exhibit exacerbated symptoms of gestational hypertension, placental abruption, preterm labor, and venous thromboembolism. Although this disease is manageable, it has the potential to adversely impact maternal and child health on a national level. The chances of severe complications in the pregnant state affecting both mother and fetus attract due attention of health services towards redefining and researching this disease and its management frequently. The literature review on the following situation advocates the general treatment to be observed under the headings of preconceptual care, strengthened antenatal care, strict intranatal care, and compliant post-natal care. Preconceptually, genetic screening of couples, with education on the adverse effects of the disease, comes as the first line of management. Newer facilities like preimplantation genetic diagnosis and celocentesis may even allow for early diagnosis as well as help patients who do not wish to terminate the pregnancy by selective transfer of unaffected embryos. This may be combined with an extensive evaluation of the psychosocial aspect and socioeconomic status of couples who administer vaccines as prophylaxis for preventable diseases. Strengthening antenatal care is associated with routine blood investigations for every registered antenatal patient with adequate awareness about the conditions that precipitate the crisis. All patients should be prophylactically treated with appropriate doses of aspirin, iron, folic acid, and multivitamins. Radiological examinations by ultrasonography may be used to monitor placenta previa, abruption, or preterm labor. Later in pregnancy, it should be recommended to perform biophysical profiling and assessment of umbilical artery flow. Intranatal care deals with strict-term institutional delivery of all sickle cell-diseased mothers with a preference for vaginal delivery. Post-natal care requires a precise assessment of blood loss during labor to initiate transfusion therapy as soon as needed. Exclusive breastfeeding, with the importance of early initiation of it, must be emphasized. Screening of neonates as quickly as possible must be done for hemoglobinopathies. Through this review, authors are trying to make aware of the complications that can be faced during pregnancy in SCD patients, its prevention, and its treatment according to various new guidelines and research available.
PubMed: 37525766
DOI: 10.7759/cureus.41165 -
The Journal of Maternal-fetal &... Dec 2023To evaluate the risk of recurrence of severe placenta-mediated pregnancy complications and compare the efficacy of two different anti-thrombotic regimens in women with a... (Observational Study)
Observational Study
Placenta-mediated pregnancy complications in women with a history of late fetal loss and placental infarction without thrombophilia: risk of recurrence and efficacy of pharmacological prophylactic interventions. A 10-year retrospective study.
PURPOSE
To evaluate the risk of recurrence of severe placenta-mediated pregnancy complications and compare the efficacy of two different anti-thrombotic regimens in women with a history of late fetal loss without thrombophilia.
PATIENTS AND METHODS
We performed a 10-year retrospective observational study (2008-2018) analyzing a cohort of 128 women who suffered from pregnancy fetal loss (>20 weeks of gestational age) with histological evidence of placental infarction. All the women tested negative for congenital and/or acquired thrombophilia. In their subsequent pregnancies, 55 received prophylaxis with acetylsalicylic acid (ASA) only and 73 received ASA plus low molecular weight heparin (LMWH).
RESULTS
Overall, one-third of all pregnancies (31%) had adverse outcomes related to placental dysfunction: pre-term births (25% <37 weeks, 5.6% <34 weeks), newborns with birth weight <2500 g (17%), and newborns small for gestational age (5%). The prevalence of placental abruption, early and/or severe preeclampsia, and fetal loss >20 weeks were 6%, 5%, and 4% respectively. We found a risk reduction for combination therapy (ASA plus LMWH) compared with ASA alone for delivery <34 weeks (RR 0.11, 95% CI: 0.01-0.95 = 0.045) and a trend for the prevention of early/severe preeclampsia (RR 0.14, 95% CI: 0.01-1.18, = 0.0715), while no statistically significant difference was observed for composite outcomes (RR 0.51, 95%CI: 0.22-1.19, = 0.1242). An absolute risk reduction of 5.31% was observed for the ASA plus LMWH group. Multivariate analysis confirmed a risk reduction for delivery <34 weeks (RR 0.32, 95% CI 0.16-0.96 = 0.041).
CONCLUSION
In our study population, the risk of recurrence of placenta-mediated pregnancy complications is substantial, even in the absence of maternal thrombophilic conditions. A reduction of the risk of delivery <34 weeks was detected in the ASA plus LMWH group.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Placenta; Retrospective Studies; Pre-Eclampsia; Heparin, Low-Molecular-Weight; Placenta Diseases; Thrombophilia; Abortion, Spontaneous; Aspirin; Infarction
PubMed: 36860098
DOI: 10.1080/14767058.2023.2183748 -
Aging Oct 2023Placental growth factor (PlGF), an important polypeptide hormone, plays an important regulatory role in various physiological processes. Observational studies have shown...
OBJECTIVE
Placental growth factor (PlGF), an important polypeptide hormone, plays an important regulatory role in various physiological processes. Observational studies have shown that PlGF is associated with the risk of coronary heart disease (CHD). However, the causal association between PlGF and CHD is unclear at present. This study aimed to investigate the causal association between genetically predicted PlGF levels and CHD.
METHODS
Single nucleotide polymorphisms (SNPs) associated with PlGF were selected as instrumental variables (IVs) to evaluate the causal association between genetically predicted circulating PlGF levels and CHD risk by two-sample Mendelian randomization (MR).
RESULTS
Inverse variance weighted (IVW) analysis showed that there was a suggestive causal association between genetically predicted PlGF level and the risk of CHD (OR = 0.79, 95% CI: 0.66-0.95, = 0.011) overall. In addition, PlGF levels had a significant negative causal association with the risk of myocardial infarction (OR = 0.83, 95% CI: 0.72-0.95, = 0.007). A negative correlation trend was found between PlGF level and the risk of angina pectoris (OR = 0.89, 95% CI: 0.79-1.01, = 0.067). In addition, PlGF levels had a significant negative association with the risk of unstable angina pectoris (OR = 0.78, 95% CI: 0.64-0.94, = 0.008). PlGF levels were negatively correlated with CHD events with suggestive significance (OR = 0.89, 95% CI: 0.80-0.99, = 0.046).
CONCLUSION
Genetically predicted circulating PlGF levels are causally associated with the risk of CHD, especially acute coronary syndrome, and PlGF is a potential therapeutic target for CHD.
Topics: Female; Humans; Placenta Growth Factor; Mendelian Randomization Analysis; Coronary Disease; Angina Pectoris; Myocardial Infarction; Polymorphism, Single Nucleotide; Genome-Wide Association Study
PubMed: 37787982
DOI: 10.18632/aging.205061 -
Romanian Journal of Morphology and... 2023The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain relatively unknown.
BACKGROUND
The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain relatively unknown.
AIM
We present this original paper where we analyzed 60 parturients, at term, 30 without associated infection (C-) and 30 with associated infection (C+), present at birth.
METHODS
We analyzed the blood count and placental microscopic structure through classical and immunohistochemical staining and observed the placental areas affected by the presence of SARS-CoV-2.
RESULTS
SARS-CoV-2 infection was accompanied by a decrease in the number of lymphocytes, the number of platelets and the presence of placental structural changes, identifying extensive areas of amyloid deposits, placental infarcts, vascular thrombosis, syncytial knots, with a decrease in placental vascular density and the presence of infection in the cells located at decidual level, at syncytiotrophoblast level and at the level of the cells of the chorionic plate, still without overcoming this barrier and without causing any fetal infection in the analyzed cases.
CONCLUSIONS
This study shows that the invasion of SARS-CoV-2 in the placenta can produce significant structural changes, with a decrease in placental vascular density that can have significant implications on proper fetal perfusion. Also, the presence of immunoreactivity at the level of decidua, the placental villi, as well as the chorionic plate proves that the virus can overcome the maternal-fetal barrier. However, in the analyzed cases there were no fetal infections at birth, which may show that local placental factors can be a protective filter for the fetus.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Placenta; SARS-CoV-2; COVID-19; Immune System; Placenta Diseases
PubMed: 38184836
DOI: 10.47162/RJME.64.4.12 -
Medical Research Archives Aug 2023To compare macro- and microscopic features of the placenta with the pulsatility index (PI) of the uterine (UtA), umbilical (UA) and middle cerebral arteries at 20-24-...
AIMS
To compare macro- and microscopic features of the placenta with the pulsatility index (PI) of the uterine (UtA), umbilical (UA) and middle cerebral arteries at 20-24- and 34-38-weeks' gestation, and with birthweight z-scores (BWZS).
METHODS
Recruitment for the Safe Passage Study, which investigated the association of alcohol and tobacco use with stillbirth and sudden infant death syndrome, occurred from August 2007 to January 2015 at community clinics in Cape Town, South Africa. The population represents a predominantly homogenous population of pregnant women from a low socioeconomic residential area. This study is a further analysis of the data of the Safe Passage Study. It consists of 1205 singleton pregnancies for which placental histology was available, of whom 1035 had a known BWZS and 1022 and 979 had fetoplacental Doppler examinations performed at Tygerberg Academic Hospital at 20-24 and 34-38 weeks respectively. Features of the placenta were assessed according to international norms.
RESULTS
Significantly higher ORs for the presence of individual and combined features of maternal vascular malperfusion (MVM) were found with lower BWZS and higher UtA PI values, more consistently than with higher UA PI values. Strongest associations were for a small placenta for gestational age (UtA OR 4.86 at 20-24 and 5.92 at 34-38 weeks; UA OR 5.33 at 20-24 and 27.01 at 34-38 weeks; low BWZS OR 0.31), for accelerated maturation (UtA OR 11.68 at 20-24 weeks and 18.46 at 34-38 weeks; low BWZS 0.61), for macroscopic infarction (UtA OR 6.08 at 20-24 weeks; UA OR 17.02 at 34-38 weeks; low BWZS OR 0.62) and for microscopic infarction (UtA OR 6.84 at 20-24 and 10.9 at 34-38 weeks; low BWZS OR 0.62).
CONCLUSION
There is considerable variability in the associations between individual features of MVM and increased UtA or UA PI and low BWZS. Although all MVM features currently carry equal weight in defining the condition of MVM, our data suggest that some should carry more weight than others. Macroscopic examination of the placenta may be helpful in identifying placental insufficiency as a small placenta for gestational age and macroscopic infarction were the features most strongly associated with outcomes.
PubMed: 37712063
DOI: 10.18103/mra.v11i8.4238 -
Life (Basel, Switzerland) Dec 2023Intrauterine fetal death (IUFD) is defined as death of the fetus after the 20th week of gestation. Despite regular monitoring the incidence of IUFD remains high. This...
INTRODUCTION
Intrauterine fetal death (IUFD) is defined as death of the fetus after the 20th week of gestation. Despite regular monitoring the incidence of IUFD remains high. This study aims to assess the incidence and maternal conditions associated with IUFD over term pregnancies in a twelve-year period.
MATERIALS AND METHODS
A retrospective descriptive study was conducted on a population of women in whom IUFD was diagnosed in a term pregnancy during the period from January 2010 to December 2022. The study was at the Clinic for Obstetrics and Gynecology, University Clinic Centre of Serbia. The analyses included the number of deliveries, live births, and stillbirths, as well as maternal, fetal, and placental conditions associated with the risk of IUDF. The statistical analysis involved descriptive statistical methods and one sample proportion.
RESULTS
The average age of the patients was 30 years. Most patients had secondary and higher education, and 70% of patients had regular pregnancy monitoring; 53.33% were primiparous and pregnancies occurred spontaneously. IUFD mainly occurred in the 39th week of gestation. In total, 38.3% had one to two associated diseases, 5% more than three, and 58.33% were healthy. Recurrence of IUFD was reported by 10% of patients, while 8.33% had a history of spontaneous abortion. Over 80% of placental histopathological findings indicated some pathology (e.g., infarction, infections, placental abruption).
CONCLUSIONS
The most significant risk factors for IUFD in term pregnancies in our population during the study period were hypertensive syndrome in pregnancy, obesity and gestational diabetes. Pathological findings on the placenta were more common in our study group than is usually reported with infractions of placental tissue being the most common, even in healthy women.
PubMed: 38137921
DOI: 10.3390/life13122320 -
Cytokine & Growth Factor Reviews Dec 2023Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains a puzzling clinical entity. It is characterized by clinical evidence of myocardial...
Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains a puzzling clinical entity. It is characterized by clinical evidence of myocardial infarction (MI) with normal or near-normal coronary arteries in angiography. Given the complex etiology including multiple possible scenarios with varied pathogenetic mechanisms, profound investigation of the plausible biomarkers of MINOCA may bring further pathophysiological insights and novel diagnostic opportunities. Cytokines have a great diagnostic potential and are used as biomarkers for many diseases. An unusual trio of visfatin, placental growth factor (PlGF) and fractalkine (CX3CL1) can directly promote vascular dysfunction, inflammation and angiogenesis through the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. They are redundant in physiological processes and become overexpressed in the pathomechanisms underlying MINOCA. The knowledge about their concentration might serve as a valuable diagnostic and/or therapeutic tool for assessing vascular endothelial function. Here we analyze the current knowledge on visfatin, PlGF and CX3CL1 in the context of MINOCA and present the novel clinical implications of their combined expression as predictors or indicators of this condition.
Topics: Humans; Biomarkers; Chemokine CX3CL1; Coronary Angiography; Coronary Artery Disease; Cytokines; MINOCA; Myocardial Infarction; Nicotinamide Phosphoribosyltransferase; Placenta Growth Factor; Risk Factors
PubMed: 37679252
DOI: 10.1016/j.cytogfr.2023.08.009